Proton-motive force of the mitochondrial inner membrane (PMF)

The **proton-motive force of the mitochondrial inner membrane** (PMF) is not a discrete molecule or classical receptor, but a physicochemical gradient generated by the electron transport chain (ETC) across the mitochondrial inner membrane during oxidative phosphorylation. It is comprised of both an electrical potential (Δψ) and a chemical gradient (ΔpH) formed as protons are pumped from the matrix to the intermembrane space by ETC complexes. The PMF drives ATP synthesis via ATP synthase, powers metabolite and ion exchange, and regulates multiple aspects of cell physiology, including reactive oxygen species production and thermogenesis. Disruption or modulation of PMF plays roles in various diseases and is targeted experimentally by several drugs and uncoupling agents. However, as a *bioenergetic state or process* rather than a molecular target, it is **not properly categorized as a single drug target** like a receptor, enzyme, or transporter[1][2][3][4][5][6]. Additional notes: - The entry is **incorrect as a molecular drug target**: PMF is a property/process of the mitochondrial inner membrane, not a single protein, receptor, or well-defined biomolecule that can be unambiguously targeted. - Modulators of PMF act on components that generate or dissipate the PMF (e.g., ETC complexes, uncoupling proteins, ATP synthase), rather than the PMF itself.

Other names

protonmotive forceproton motive force (Δp)mitochondrial proton gradientmitochondrial membrane potential (for Δψ component)pmf

Modulation of proton leak (uncoupling), inhibition of ATP synthase, ETC inhibition, dissipation of the gradient, alteration of electron flow